Patch-based physiological sensor

ABSTRACT

The invention provides a neck-worn sensor for simultaneously measuring a blood pressure (BP), pulse oximetry (SpO2), and other vital signs and hemodynamic parameters from a patient. The neck-worn sensor features a sensing portion having a flexible housing that is worn entirely on the patient&#39;s chest and encloses a battery, wireless transmitter, and all the sensor&#39;s sensing and electronic components. It measures electrocardiogram (ECG), impedance plethysmogram (IPG), photoplethysmogram (PPG), and phonocardiogram (PCG) waveforms, and collectively processes these to determine the vital signs and hemodynamic parameters. The sensor that measures PPG waveforms also includes a heating element to increase perfusion of tissue on the chest.

BACKGROUND AND FIELD OF THE INVENTION 1. Field of the Invention

The invention relates to the use of systems that measure physiologicalparameters from patients located, for example, in hospitals, clinics,and the home.

2. General Background

There are a number of physiological parameters that can be assessed bymeasuring biometric signals from a patient. Some signals, such aselectrocardiogram (ECG), impedance plethysmogram (IPG),photoplethysmogram (PPG), and phonocardiogram (PCG) waveforms, aremeasured with sensors (e.g. electrodes, optics, microphones) thatconnect or attach directly to the patient's skin. Processing of thesewaveforms yields parameters such as heart rate (HR), heart ratevariability (HRV), respiration rate (RR), pulse oximetry (SpO2), bloodpressure (BP), stroke volume (SV), cardiac output (CO), and parametersrelated to thoracic impedance, for example thoracic fluid content(FLUIDS). Many physiological conditions can be identified from theseparameters when they are obtained at a single point in time; others mayrequire continuous assessment over long or short periods of time toidentify trends in the parameters. In both cases, it is important toobtain the parameters with high repeatability and accuracy.

3. Known Devices and Relevant Physiology

Some devices that measure ECG waveforms are worn entirely on thepatient's body. These devices often feature simple, patch-type systemsthat include both analog and digital electronics connected directly tounderlying electrodes. Typically, these systems measure HR, HRV, RR,and, in some cases, posture, motion, and falls. Such devices are oftenprescribed for relatively short periods of time, such as a time periodranging from a few days to several weeks. They are typically wireless,and usually include technologies such as Bluetooth® transceivers totransmit information over a short range to a second device, which mayinclude a cellular radio to transmit the information to a web-basedsystem.

Bioimpedance medical devices measure SV, CO, and FLUIDS by sensing andprocessing time-dependent ECG and IPG waveforms. Typically, thesedevices connect to patients through disposable electrodes adhered atvarious locations on a patient's body. Disposable electrodes thatmeasure ECG and IPG waveforms are typically worn on the patient's chestor legs and include: i) a conductive hydrogel that contacts the patient;ii) a Ag/AgCl-coated eyelet that contacts the hydrogel; iii) aconductive metal post that connects the eyelet to a lead wire or cableextending from the device; and iv) an adhesive backing that adheres theelectrode to the patient. Medical devices that measure BP, includingsystolic (SYS), diastolic (DIA), and mean (MAP) BP, typically usecuff-based techniques called oscillometry or auscultation, orpressure-sensitive catheters than are inserted in a patient's arterialsystem. Medical devices that measure SpO2 are typically optical sensorsthat clip onto a patient's finger or earlobes, or attach through anadhesive component to the patient's forehead.

SUMMARY OF THE INVENTION

In view of the foregoing, it would be beneficial to improve themonitoring of patients in hospitals, clinics, and the home with abody-worn sensor. The sensor described herein is such a device: aneck-worn sensor resembling a conventional necklace or collar thatnon-invasively measures vital signs such as HR, HRV, RR, SpO2, TEMP, andBP, along with complex hemodynamic parameters such as SV, CO, andFLUIDS. The neck-worn sensor adheres to a patient's chest andcontinuously and non-invasively measures the above-mentioned parameterswithout cuffs and wires. In this way, it simplifies traditionalprotocols for taking such measurements, which typically involve multiplemachines and can take several minutes to accomplish. The neck-wornsensor wirelessly transmits information to an external gateway (e.g.tablet, smartphone, or non-mobile, plug-in system) which can integratewith existing hospital infrastructure and notification systems, such asa hospital electronic medical records (EMR) system. With such a system,caregivers can be alerted to changes in vital signs, and in response canquickly intervene to help deteriorating patients. The neck-worn sensorcan additionally monitor patients from locations outside the hospital.

More particularly, the invention features a neck-worn sensor thatmeasures the following parameters from a patient: HR, PR, SpO2, RR, BP,TEMP, FLUIDS, SV, CO, and a set of parameters sensitive to bloodpressure and systemic vascular resistance called pulse arrival time(PAT) and vascular transit time (VTT).

The neck-worn sensor also includes a motion-detecting accelerometer,from which it can determine motion-related parameters such as posture,degree of motion, activity level, respiratory-induced heaving of thechest, and falls. Such parameters could determine, for example, apatient's posture or movement during a hospital stay. The neck-wornsensor can operate additional algorithms to process the motion-relatedparameters to measure vital signs and hemodynamic parameters when motionis minimized and below a predetermined threshold, thereby reducingartifacts. Moreover, the neck-worn sensor estimates motion-relatedparameters such as posture to improve the accuracy of calculations forvital signs and hemodynamic parameters.

Disposable electrodes on a bottom surface of the neck-worn sensor secureit to the patient's body without requiring bothersome cables. Theelectrodes measure ECG and IPG waveforms. They easily connect (anddisconnect) to circuit boards contained within the sensor by means ofmagnets. The magnets are electrically connected to the circuit boards toprovide signal-conducting electrical couplings. Prior to use, theelectrodes are simply held near the circuit boards, and magneticattraction causes the electrode patches to snap into proper position,thereby ensuring proper positioning of the electrodes on the patient'sbody.

Using light-emitting diodes (LEDs) operating in the red (e.g. 660 nm)and infrared (e.g. 900 nm) spectral regions, the neck-worn sensormeasures SpO2 by pressing lightly against capillary beds in thepatient's chest. A heating element on the bottom surface of theneck-worn sensor contacts the patient's chest and gently warms theunderlying skin, thereby increasing perfusion of the tissue. Operatingwith reflection-mode optics, the neck-worn sensor measures PPG waveformswith both red and infrared wavelengths. SpO2 is processed fromalternating and static components of these waveforms, as is described inmore detail below.

The neck-worn sensor measures all of the above-mentioned propertieswhile featuring a comfortable, easy-to-wear form factor. It islightweight (about 30 grams) and powered with a rechargeable battery.During use, it rests on the patient's chest, where the disposableelectrodes hold it in place, as described in more detail below. Thepatient's chest is a location that is unobtrusive, comfortable, removedfrom the hands, and able to hold the sensor without being noticeable tothe patient. It is also relatively free of motion compared to appendagessuch as the hands and fingers, and thus a sensor affixed to the chestregion minimizes motion-related artifacts. Such artifacts arecompensated for, to some degree, by the accelerometer within the sensor.Because the neck-worn sensor is a small and therefore considerably lessnoticeable or obtrusive than various other physiological sensor devices,emotional discomfort over wearing a medical device over an extendedperiod of time is reduced, thereby fostering long-term patientcompliance for use of this device within a monitoring regimen.

Given the above, in one aspect, the invention provides a neck-wornsensor for simultaneously measuring BP and SpO2 from a patient. Theneck-worn sensor features a sensing portion having a flexible housingthat is worn entirely on the patient's chest and encloses a battery,wireless transmitter, and all the sensor's sensing and electroniccomponents. The sensor measures ECG, IPG, PPG, and PCG waveforms, andcollectively processes these determine BP and SpO2. The sensor thatmeasures PPG waveforms includes a heating element to increase perfusionof tissue on the chest.

On its bottom surface, the flexible housing includes an analog opticalsystem, located proximal to one pair of the electrode contact points,that features a light source that generates radiation in both the redand infrared spectral ranges. This radiation separately irradiates aportion of the patient's chest disposed underneath the flexible housing.A photodetector detects the reflected radiation in the differentspectral ranges to generate analog red-PPG and infrared-PPG waveforms.

A digital processing system disposed within the flexible housingincludes a microprocessor and an analog-to-digital converter, and isconfigured to: 1) digitize the analog ECG waveform to generate a digitalECG waveform, 2) digitize the analog impedance waveform to generate adigital impedance waveform, 3) digitize the analog red-PPG waveform togenerate a digital red-PPG waveform, 4) digitize the analog infrared-PPGwaveform to generate a digital infrared-PPG waveform, and 5) digitizethe analog PCG waveform to generate a digital PCG waveform. Once thesewaveforms are digitized, numerical algorithms operating in embeddedcomputer code called ‘firmware’ process them to determine the parametersdescribed herein.

In another aspect, the invention provides a neck-worn sensor formeasuring a PPG waveform from a patient. The neck-worn sensor includes ahousing worn on the patient's chest, and a heating element attached tothe bottom surface of the housing so that, during use, it contacts andheats an area of the patient's chest. An optical system is located on abottom surface of the housing and proximal to the heating element, andincludes a light source that generates optical radiation that irradiatesthe area of the patient's chest during a measurement. The sensor alsofeatures a temperature sensor in direct contact with the heatingelement, and a closed-loop temperature controller within the housing andin electrical contact with the heating element and the temperaturesensor. During a measurement, the closed-loop temperature controllerreceives a signal from the temperature sensor and, in response, controlsan amount of heat generated by the heating element. A photodetectorwithin the optical system generates the PPG waveform by detectingradiation that reflects off the area of the patient's chest after it isheated by the heating element.

Heating tissue that yields the PPG waveform typically increases bloodflow (i.e. perfusion) to the tissue, thereby increasing the amplitudeand signal-to-noise ratio of the waveform. This is particularlyimportant for measurements made at the chest, where signals aretypically significantly weaker than those measured from moreconventional locations, such as the fingers, earlobes, and forehead.

In embodiments, the heating element features a resistive heater, such asa flexible film, metallic material, or polymeric material (e.g. Kapton®)that may include a set of embedded electrical traces that increase intemperature when electrical current passes through them. For example,the electrical traces may be disposed in a serpentine pattern tomaximize and evenly distribute the amount of heat generated during ameasurement. In other embodiments, the closed-loop temperaturecontroller includes an electrical circuit that applies an adjustablepotential difference to the resistive heater that is controlled by amicroprocessor. Preferably, the microcontroller adjusts the potentialdifference it applies to the resistive heater so that its temperature isbetween 40-45° C.

In embodiments, the flexible-film heating element features an openingthat transmits optical radiation generated by the light source so thatit irradiates an area of the patient's chest disposed underneath thehousing. In similar embodiments, the flexible film features a similaropening or set of openings that transmit optical radiation reflectedfrom the area of the patient's chest so that it is received by thephotodetector.

In still other embodiments, the housing further includes an ECG sensorthat features a set of electrode leads, each configured to receive anelectrode, that connect to the housing and electrically connect to theECG sensor. For example, in embodiments, a first electrode lead isconnected to one side of the housing, and a second electrode lead isconnected to an opposing side of the housing. During a measurement, theECG sensor receives ECG signals from both the first and secondelectrodes leads, and, in response, processes the ECG signals todetermine an ECG waveform.

In another aspect, the invention provides a necklace-shaped sensor formeasuring PPG and ECG waveforms from a patient that features an opticalsensor, heating element, and temperature sensor similar to thatdescribed above. The sensor also includes a closed-loop temperaturecontroller within the housing and in electrical contact with the heatingelement, the temperature sensor, and the processing system. Theclosed-loop temperature controller is configured to: 1) receive a firstsignal from the temperature sensor; 2) receive a second signal from theprocessing system corresponding to the second fiducial marker; 3)collectively process the first and second signals to generate a controlparameter; and 4) control an amount of heat generated by the heatingelement based on the control parameter.

In embodiments, a software system included in the processing systemdetermines a first fiducial marker within the ECG waveform that is oneof a QRS amplitude, a Q-point, a R-point, an S-point, and a T-wave.Similarly, the software system determines a second fiducial marker thatis one of an amplitude of a portion of the PPG waveform, a foot of aportion of the PPG waveform, and a maximum amplitude of a mathematicalderivative of the PPG waveform.

In embodiments, the closed-loop temperature controller features anadjustable voltage source, and is configured to control an amount ofheat generated by the heating element by adjusting the voltage source,e.g. the amplitude or frequency of a voltage generated by the voltagesource.

In another aspect, the invention provides a similar necklace-shapedsensor that is worn on a patient's chest and measures PPG waveforms fromthe patient, and from these SpO2 values. The sensor features a similarheating element, temperature, closed-loop temperature controller, andoptical system as described above. Here, the optical system generatesoptical radiation in both the red and infrared spectral regions. Thesensor also includes an ECG sensor with at least two electrode leads andan ECG circuit that generates an ECG waveform. During a measurement, aprocessing system featuring a software system analyzes the ECG waveformto identify a first fiducial marker, and based on the first fiducialmarker, identifies a first set of fiducial markers within the red PPGwaveform, and a second set of fiducial markers within the infrared PPGwaveform. The processing system then collectively processes the firstand second set of fiducial markers to generate the SpO2 value.

In embodiments, for example, the first set of fiducials identified bythe software system features an amplitude of a baseline of the red PPGwaveform (RED(DC)) and an amplitude of a heartbeat-induced pulse withinthe red PPG waveform (RED(AC)), and the second set of fiducialsidentified by the software system features an amplitude of a baseline ofthe infrared PPG waveform (IR(DC)) and an amplitude of aheartbeat-induced pulse within the infrared PPG waveform (IR(AC)). Thesoftware system can be further configured to generate the SpO2 valuefrom a ratio of ratios (R) by analyzing the RED(DC), RED(AC), IR(DC),and IR(AC) using the following equations, or mathematical equivalentsthereof:

$R = \frac{{{RED}({AC})}/{{RED}({DC})}}{{{IR}({AC})}/{{IR}({DC})}}$${{SpO}\; 2} = \frac{k_{1} - {k_{2} \times R}}{k_{3} - {k_{4} \times R}}$where k₁, k₂, k₃, and k₄ are pre-determined constants. Typically, theseconstants are determined during a clinical study called a ‘breathe-downstudy’ using a group of patients. During the study, the concentration ofoxygen supplied to the patients is gradually lowered in sequential‘plateaus’ so that their SpO2 values changes from normal values (near98-100%) to hypoxic values (near 70%). As the concentration of oxygen islowered, reference SpO2 values are typically measured at each plateauwith a calibrated oximeter or a machine that measures oxygen contentfrom aspirated blood. These are the ‘true’ SpO2 values. R values arealso determined at each plateau from PPG waveforms measured by theneck-worn sensor. The pre-determined constants k₁, k₂, k₃, and k₄ canthen be determined by fitting these data using equations shown above.

In other aspects, the invention provides a necklace-shaped sensorsimilar to that described above, that also includes an acoustic sensorfor measuring PCG waveforms. Here, the sensor is mated with a single-usecomponent that temporarily attaches to the sensor's housing and featuresa first electrode region positioned to connect to the first electrodecontact point, a second electrode region positioned to connect to thesecond electrode contact point, and an impedance-matching regionpositioned to attach to the acoustic sensor.

In embodiments, the impedance-matching region comprises a gel or plasticmaterial, and has an impedance at 100 kHz of about 220Ω. The acousticsensor can be a single microphone or a pair of microphones. Typically,the sensor includes an ECG sensor that yields a signal that is thenprocessed to determine a first fiducial point (e.g. a Q-point, R-point,S-point, or T-wave of a heartbeat-induced pulse in the ECG waveform). Aprocessing system within the sensor processes the PCG waveform todetermine the second fiducial point, which is either the S1 heart soundor S2 heart sound associated with a heartbeat-induced pulse in the PCGwaveform. The processing system then determines a time differenceseparating the first fiducial point and the second fiducial point, anduses this time difference to determine the patient's blood pressure.Typically, a calibration measurement made by a cuff-based system is usedalong with the time difference to determine blood pressure.

In embodiments, the processor is further conjured to determine afrequency spectrum of the second fiducial point (using, e.g., a FourierTransform), and then uses this to determine the patient's bloodpressure.

In yet another aspect, the invention provides a chest-worn sensorsimilar to that described above. Here, the sensor features an opticalsystem, located on a bottom surface of the sensor's housing, thatincludes: 1) a light source that generates optical radiation thatirradiates an area of the patient's chest disposed underneath thehousing; and 2) a circular array of photodetectors that surround thelight source and detect optical radiation that reflects off the area ofthe patient's chest. As before, the area is heated with a heatingelement prior to a measurement.

In another aspect, the invention provides a neck-worn sensor formeasuring a PPG waveform from a patient. The neck-worn sensor features ahousing that is curved and flexible with unconnected first and seconddistal ends. During use, the housing drapes around the patient's neck sothat the first distal end rests on the right-hand side of the patient'schest, and the second distal end rests on the left-hand side of thepatient's chest. A heating element attaches to the bottom surface ofeither the first or second distal end of the housing so that it contactsand heats an area of the patient's chest when the housing is worn on thepatient's chest. An optical system connected to the heating elementfeatures a light source that generates optical radiation that irradiatesthe area of the patient's chest. The sensor also includes a temperaturesensor in direct contact with the heating element, and a closed-looptemperature controller within the housing and in electrical contact withboth the heating element and the temperature sensor. During use, theclosed-loop temperature controller receives a signal from thetemperature sensor and, in response, controls an amount of heatgenerated by the heating element. A photodetector within the opticalsystem generates a PPG waveform by detecting radiation that reflects offthe area of the patient's chest after it is heated by the heatingelement.

In yet another aspect, the invention provides a neck-worn sensor formeasuring PPG, PCG, and ECG waveforms from a patient. Here, the sensorfeatures a housing composed of: 1) a first enclosure component featuringa first distal end; 2) a second enclosure component featuring a seconddistal end; and 3) a curved component connected on one side to the firstenclosure component at a location opposite the first distal end, and onits opposing side to the second enclosure component at a locationopposite to the second distal end. Collectively, the combined firstenclosure component, second enclosure component, and curved componentform a curved, contiguous housing that is approximately C-shaped andfeatures a contiguous length (traced from one distal end to the other)between 590 and 630 mm. The resultant housing is configured so that thefirst and second distal ends remain unconnected and, during use, thecurved component drapes around the patient's neck while the first distalend rests on the right-hand side of the patient's chest and the seconddistal end rests on the left-hand side of the patient's chest.

An optical sensor is disposed on the first distal end, and includes alight source for irradiating a portion of the patient's chest, and aphotodetector for detecting radiation that reflects off the patient'schest to generate the PPG waveform. An acoustic sensor is disposed onthe second distal end, and includes a sound-detecting sensor thatdetects heart sounds from the patient's chest to generate the PCGwaveform.

The housing includes a first set of electrode leads disposed on thefirst distal end that connect to a first set of adhesive electrodes tosecure the optical sensor to the patient's chest, and a second set ofelectrode leads disposed on the second distal end that connect to asecond set of adhesive electrodes to secure the acoustic sensor to thepatient's chest. An ECG sensor electrically connects to the first andsecond set of electrode leads, and is configured to receive bio-electricsignals measured from the patient's chest by the first and second setsof adhesive electrodes and process them to determine the ECG waveform.

Advantages of the invention should be apparent from the followingdetailed description, and from the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic drawing showing a patient wearing a neck-wornsensor according to the invention;

FIG. 2A is a photograph of a front surface of the neck-worn sensor shownin FIG. 1.

FIG. 2B is a photograph of a back surface of the neck-worn sensor shownin FIG. 1.

FIG. 3A is a photograph of a back surface of the neck-worn sensor shownin FIG. 1, with the optical sensor emphasized;

FIG. 3B is a schematic swing of the optical sensor shown in FIG. 3A;

FIG. 4 is an exploded drawing of the optical sensor;

FIG. 5 is drawing a patient lying in a hospital bed and wearing theneck-worn sensor according to the invention, with the neck-worn sensortransmitting information through a gateway to a cloud-based system;

FIG. 6A is a time-dependent plot of an ECG waveform collected from apatient using a sensor similar to the neck-worn sensor of the invention,along with ‘x’ symbols marking fiducial points in the waveform;

FIG. 6B is a time-dependent plot of a PCG waveform collectedsimultaneously and from the same patient as the ECG waveform shown inFIG. 6A using a sensor similar to the neck-worn sensor of the invention,along with ‘x’ symbols marking fiducial points in the waveform;

FIG. 6C is a time-dependent plot of a PPG waveform collectedsimultaneously and from the same patient as the ECG waveform shown inFIG. 6A using a sensor similar to the neck-worn sensor of the invention,along with ‘x’ symbols marking fiducial points in the waveform;

FIG. 6D is a time-dependent plot of a IPG waveform collectedsimultaneously and from the same patient as the ECG waveform shown inFIG. 6A using a sensor similar to the neck-worn sensor of the invention,along with ‘x’ symbols marking fiducial points in the waveform;

FIG. 6E is a time-dependent plot of a mathematical derivative of the IPGwaveform shown in FIG. 6D, along with ‘x’ symbols marking fiducialpoints in the waveform;

FIG. 7A is a time-dependent plot of ECG and PCG waveforms generatedusing a sensor similar to the neck-worn sensor from a single heartbeatfrom a patient, along with circular symbols marking fiducial points inthese waveforms and indicating a time interval related to S2;

FIG. 7B is a time-dependent plot of an ECG waveform and the mathematicalderivative of an IPG waveform generated using a sensor similar to theneck-worn sensor from a single heartbeat from a patient, along withcircular symbols marking fiducial points in these waveforms andindicating a time interval related to B;

FIG. 7C is a time-dependent plot of an ECG waveform and the mathematicalderivative of an IPG waveform generated using a sensor similar to theneck-worn sensor from a single heartbeat from a patient, along with anarrow symbol marking a amplitude related to (dZ/dt)_(max);

FIG. 7D is a time-dependent plot of ECG and PPG waveforms generatedusing a sensor similar to the neck-worn sensor from a single heartbeatfrom a neck-worn patient, along with circular symbols marking fiducialpoints in these waveforms and indicating a time interval related to PAT;

FIG. 7E is a time-dependent plot of an ECG waveform and the mathematicalderivative of an IPG waveform generated using a sensor similar to theneck-worn sensor from a single heartbeat from a patient, along withcircular symbols marking fiducial points in these waveforms andindicating a time interval related to C;

FIG. 7F is a time-dependent plot of ECG and IPG waveforms generatedusing a sensor similar to the neck-worn sensor from a single heartbeatfrom a patient, along with an arrow symbol marking an amplitude relatedto Z₀;

FIG. 8A is a time-dependent plot of a PPG waveform measured with theoptical sensor of FIG. 3B before heat is applied to an underlyingsurface of a patient's skin;

FIG. 8B is a time-dependent plot of a PPG waveform measured with theoptical sensor of FIG. 3B after heat is applied to an underlying surfaceof a patient's skin;

FIG. 9 is a flow chart showing an algorithm used by the neck-worn sensorto measure cuffless BP;

FIG. 10 is a table showing results from a clinical trial conducted on 21subjects that compared a cuffless BP measurement made by a sensorsimilar to the neck-worn sensor of FIG. 1 to a reference BP measurementperformed using auscultation; and

FIG. 11 is a schematic drawing showing a patient wearing an alternateembodiment of the neck-worn sensor according to the invention.

DETAILED DESCRIPTION 1. Neck-Worn Sensor

As shown in FIGS. 1, 2A, and 2B, a neck-worn sensor 10 according to theinvention measures ECG, PPG, PCG, and IPG waveforms from a patient 12,and from these calculates vital signs (HR, HRV, SpO2, RR, BP, TEMP) andhemodynamic parameters (FLUIDS, SV, and CO) as described in detailbelow. Once this information is determined, the neck-worn sensor 10wirelessly transmits it to an external gateway, which then forwards itto a cloud-based system. In this way, a clinician can continuously andnon-invasively monitor the patient 12, who may be located in either thehospital or home.

The neck-worn sensor 10 drapes around the neck of a patient 12 like anecklace or collar. It features three primary components: 1) a firstsensing portion 33A disposed on the right-hand side of the patient'schest; 2) a second sensing portion 33B disposed on the left-hand side ofthe patient's chest; and 3) a wire-carrying component 29 that wrapsaround the back portion of the patient's neck, and encloses conductingwires that electrically connect the first sensing portion 33A and thesecond sensing portion 33B. The first sensing portion 33A includes anoptical sensor 36 that measures PPG waveforms from underlying capillarybeds in the patient's chest. The optical sensor 36 is surrounded twoelectrode leads 41, 42 that connect to adhesive electrodes and helpsecure the neck-worn sensor 10 (and particularly the optical sensor 36)to the patient 12. The electrode leads 41, 42 also collect bio-electricsignals from the patient, which are then used for ECG and IPG waveforms,as described in more detail below. The second sensing portion 33Bincludes an acoustic sensor 45 that measures sounds from the patient'sheart that, after processing, yield PCG waveforms. Similar to theoptical sensor 36, the acoustic sensor 45 is proximal to a pair ofelectrode leads 47, 48. Here, the electrode leads 47, 48 sit above theacoustic sensor 45 when the neck-worn sensor 10 is worn on the patient'schest, and are located on the opposite side of the chest from electrodeleads 41, 42. They help secure the acoustic sensor 45 to the patient,and, like electrode leads 41, 42, collect bio-electric signals from thepatient. A third electrode magnet 40 sits below the electrode leads 47,48. The electrode magnet 40 connects to an adhesive component to helpcouple the acoustic sensor 45 to the chest, but, unlike electrode leads47, 48, does not collect any bio-electric signal from the patient 12.Collectively, the three electrode leads 40, 47, 48 tightly secure theacoustic sensor 45 to the patient's chest during a measurement.

The first 33A and second 33B sensor portions are typically composed of ahard plastic material that protects circuitry components (not shown inthe figure) disposed therein. The circuitry components are typicallydisposed on rigid fiberglass circuit boards, or alternatively acombination of rigid and flexible circuit boards, with one circuit boardbeing housed in the first sensor portion 33A, and a second circuit boardhoused in the second sensor portion 33B. Electrical connections betweenthe circuit boards are made with an electrical cable (also not shown inthe figure) that solders to each of the circuit boards, and then snakesthrough the wire-carrying component 29. The first sensor portion 33Aconnects to one side of the wire-carrying component 29 through a firstflexible joint 25A, and the second sensor portion 33B connects to anopposing side of the wire-carrying component 29 through a secondflexible joint 25B. With this design, the neck-worn sensor 10 isinherently flexible and can conform to the inevitable curves in thepatient's chest. In typical embodiments, to maximize comfort, thewire-carrying component 29 is composed of a hard plastic material thatis overmolded with a soft rubber material. To accommodate patients ofdifferent sizes, the wire-carrying component 29 typically comes indifferent sizes (e.g. small, medium, and large), while the first 33A andsecond 33B sensor portions typically only come in one size. Such adesign simplifies manufacturing and control over inventory associatedwith the neck-worn sensor 10.

Referring more specifically to FIG. 2B, the neck-worn sensor 10 includesa back surface that, during use, contacts the patient's chest through aset of single-use, adhesive electrodes (not shown in the figure). Asdescribed above, the first sensor portion 33A includes two electrodeleads 41, 42, and the second sensor portion 33B includes two additionalelectrode leads 47, 48. Collectively, the electrode leads 41, 42, 47, 48form two ‘pairs’ of leads, wherein one of the leads 41, 47 in each pairinjects electrical current into the patient's chest to measure IPGwaveforms, and the other leads 42, 48 in each pair sense bio-electricalsignals that are then processed by electronics in the first 33A andsecond 33B sensor portions to determine both the ECG and IPG waveforms.

More specifically, the IPG measurement is made when thecurrent-injecting electrodes 41, 47 inject high-frequency (e.g. 100kHz), low-amperage (e.g. 4 mA) current into the patient's chest. Theelectrodes 42, 48 sense a voltage that indicates the impedanceencountered by the injected current. The voltage passes through a seriesof electrical circuits featuring analog high and low-pass filters anddifferential amplifiers to, respectively, filter out and amplify signalcomponents related to the two different waveforms. One of the signalcomponents indicates the ECG waveform; another indicates the IPGwaveform. The IPG waveform has low-frequency (DC) and high-frequency(AC) components that are further filtered out and processed, asdescribed in more detail below, to determine different impedancewaveforms.

The second sensor portion 33B includes a solid-state acoustic microphone45 that measures heart sounds from the patient 12. The heart sounds arethe ‘lub, dub’ sounds typically heard from the heart with a stethoscope;they indicate when the underlying mitral and tricuspid (S1, or ‘lub’sound) and aortic and pulmonic (S2, or ‘dub’ sound) valves close (nodetectable sounds are generated when the valves open). With signalprocessing, the heart sounds yield a PCG waveform that is used alongwith other signals to determine BP, as is described in more detailbelow. In embodiments, a second solid-state acoustic sensor (e.g. anadditional microphone) can be added near the first acoustic sensor 45,and used to provide redundancy and better detect the sounds.

The optical sensor 36 features an optical system 60 that includes anarray of photodetectors 62, arranged in a circular pattern, thatsurround a LED 61 that emits radiation in both the red and infraredspectral regions. During a measurement, sequentially emitted red andinfrared radiation from the LED 61 irradiates and reflects offunderlying tissue in the patient's chest, and is detected by the arrayof photodetectors 62. The detected radiation is modulated by bloodflowing through capillary beds in the underlying tissue. Processing thereflected radiation with electronics results in PPG waveformscorresponding to the red and infrared radiation, which as describedbelow are used to determine BP and SpO2.

The neck-worn sensor 10 also typically includes a three-axis digitalaccelerometer and a temperature sensor (not specifically identified inthe figure) to measure, respectively, three time-dependent motionwaveforms (along x, y, and z-axes) and TEMP values.

FIGS. 3A, 3B, and 4 show the optical sensor 36 in more detail. Asdescribed above, the sensor 36 features an optical system 60 with acircular array of photodetectors 62 (six unique detectors are shown inthe figure, although this number can be between three and ninephotodetectors) that surround a dual-wavelength LED 61 that emits redand infrared radiation. A heating element featuring a thin Kapton® film65 with embedded electrical conductors arranged in a serpentine patternis adhered to the bottom surface of the optical sensor 36. Otherpatterns of electrical conductors can also be used. The Kapton® film 65features cut-out portions that pass radiation emitted by the LED 61 anddetected by the photodetectors 62 after it reflects off the patient'sskin. A tab portion 67 on the thin Kapton® film 65 folds over so it canplug into a connector 74 on a fiberglass circuit board 80. Thefiberglass circuit board 80 supports and provides electrical connectionsto the array of photodetectors 62 and the LED 61. During use, softwareoperating on the neck-worn sensor 10 controls power-management circuitryon the fiberglass circuit board 80 to apply a voltage to the embeddedconductors within the thin Kapton® film 65, thereby passing electricalcurrent through them. Resistance of the embedded conductors causes thefilm 65 to gradually heat up and warm the underlying tissue. The appliedheat increases perfusion (i.e. blood flow) to the tissue, which in turnimproves the signal-to-noise ratio of the PPG waveform. This is shown inFIG. 8A, which shows a PPG waveform measured before heat is applied, andFIG. 8B, which shows a PPG waveform measured after heat is applied withthe Kapton® film 65. As is clear from the figures, heat increases theperfusion underneath the optical sensor 36. This, in turn, dramaticallyimproves the signal-to-noise ratio of heartbeat-induced pulses in thePPG waveform. This is important for the neck-worn sensor's opticalmeasurements, as PPG waveforms measured from the chest typically have asignal-to-noise ratio that is 10-100× weaker than similar waveformsmeasured from typical locations used by pulse oximeters, e.g. thefingers, earlobes, and forehead. PPG waveforms with improvedsignal-to-noise ratios typically improve the accuracy of BP and SpO2measurements made by the neck-worn sensor 10. The fiberglass circuitboard 80 also includes a temperature sensor 76 that integrates with thepower-management circuitry, allowing the software to operate in aclosed-loop manner to carefully control and adjust the appliedtemperature. Here, ‘closed-loop manner’ means that the software analyzesamplitudes of heartbeat-induced pulses the PPG waveforms, and, ifnecessary, increases the voltage applied to the Kapton® film 65 toincrease its temperature and maximize the heartbeat-induced pulses inthe PPG waveforms. Typically, the temperature is regulated at a level ofbetween 41° C. and 42° C., which has been shown to not damage theunderlying tissue, and is also considered safe by the U.S. Food and DrugAdministration (FDA).

A plastic housing 44 featuring a top portion 53 and a bottom portion 70enclose the fiberglass circuit board 80. The bottom portion 70 alsosupports the Kapton® film 65, has cut-out portions 86 that passesoptical radiation, and includes a pair of snaps 84, 85 that connect tomated components on the top portion 53. The top portion also includes apair of ‘wings’ that enclose the electrode leads 41, 42 which, duringuse, connect to the single-use, adhesive electrodes (not shown in thefigure) that secure the optical sensor 36 to the patient. Theseelectrode leads 41, 42 also measure electrical signals that are used forthe ECG and IPG measurements, as described above.

The neck-worn sensor 10 typically measures waveforms at relatively highfrequencies (e.g. 250 Hz). An internal microprocessor running firmwareprocesses the waveforms with computational algorithms to generate vitalsigns and hemodynamic parameters with a frequency of about once everyminute. Examples of algorithms are described in the following co-pendingand issued patents, the contents of which are incorporated herein byreference: “NECK-WORN PHYSIOLOGICAL MONITOR,” U.S. Ser. No. 14/975,646,filed Dec. 18, 2015; “NECKLACE-SHAPED PHYSIOLOGICAL MONITOR,” U.S. Ser.No. 14/184,616, filed Aug. 21, 2014; and “BODY-WORN SENSOR FORCHARACTERIZING PATIENTS WITH HEART FAILURE,” U.S. Ser. No. 14/145,253,filed Jul. 3, 2014.

The neck-worn sensor 10 shown in FIGS. 1, 2A, 2B, 3A, 3B, and 4 isdesigned to maximize comfort and reduce ‘cable clutter’ when deployed ona patient, while at the same time optimizing the ECG, IPG, PPG, and PCGwaveforms it measures to determine physiological parameters such as HR,HRV, BP, SpO2, RR, TEMP, FLUIDS, SV, and CO. The sensor 10 positions thefirst 33A and second 33B sensor portions so that the first pair ofelectrode leads 41, 42 are disposed on one side of the patient's heart,and the second pair of electrode leads 47, 48 are disposed on anopposite side of the patient's heart. In these locations, thebio-electrical signals are typically strong. As described above, thisconfiguration results in ideal ECG and IPG waveforms, which are thenused to calculate the physiological parameters described herein.

This neck-worn sensor's design also allows it to comfortably fit bothmale and female patients. An additional benefit of its chest-wornconfiguration is reduction of motion artifacts, which can distortwaveforms and cause erroneous values of vital signs and hemodynamicparameters to be reported. This is due, in part, to the fact that duringeveryday activities, the chest typically moves less than the hands andfingers, and subsequent artifact reduction ultimately improves theaccuracy of parameters measured from the patient.

2. Use Cases

As shown in FIG. 5, in a preferred embodiment, a neck-worn sensor 10according to the invention is designed to monitor a patient 12 during ahospital stay. Typically, the patient 12 is situated in a hospital bed11. As indicated above, in a typical use case, the neck-worn sensor 10continuously measures numerical and waveform data, and then sends thisinformation wirelessly (as indicated by arrow 77) to a gateway 22, whichcan be a number of different devices. For example, the gateway 22 can beany device operating a short-range wireless (e.g. Bluetooth®) wirelesstransmitter, e.g. a mobile telephone, tablet computer, vital signmonitor, central station (e.g. nursing station in a hospital), hospitalbed, ‘smart’ television set, single-board computer, or a simple plug-inunit. The gateway 22 wirelessly forwards information (as indicated byarrow 87) from the neck-worn sensor 10 to a cloud-based software system200. Typically, this is done with a wireless cellular radio, or onebased on an 802.11a-g protocol. There, it can be consumed and processedby a variety of different software systems, such as a hospital EMR, athird-party software system, or a data-analytics engine.

In another embodiment, the sensor collects data and then stores it ininternal memory. The data can then be sent wirelessly (e.g. to thecloud-based system, EMR, or central station) at a later time. Forexample, in this case, the gateway 22 can include an internal Bluetooth®transceiver that sequentially and automatically pairs with each sensorattached to a charging station. Once all the data collected during useare uploaded, the gateway then pairs with another sensor attached to thecharging station and repeats the process. This continues until data fromeach sensor is downloaded.

In other embodiments, the neck-worn sensor can be used to measureambulatory patients, patients undergoing dialysis in either thehospital, clinic, or at home, or patients waiting to see a doctor in amedical clinic. Here, the neck-worn sensor can transmit information inreal time, or store it in memory for transmission at a later time.

3. Determining Cuffless Blood Pressure

The neck-worn sensor determines BP by collectively processingtime-dependent ECG, IPG, PPG, and PCG waveforms, as shown in FIGS. 6A-E.Each waveform is typically characterized by a heartbeat-induced ‘pulse’that is affected in some way by BP. More specifically, embedded firmwareoperating on the neck-worn sensor processes pulses in these waveformswith ‘beatpicking’ algorithms to determine fiducial makers correspondingto features of each pulse; these markers are then processed withalgorithms, described below, to determine BP. In FIGS. 6A-E, thefiducial makers for pulses within the ECG, IPG, PPG, and PCG waveformsare indicated with ‘x’ symbols.

An ECG waveform measured by the neck-worn sensor is shown in FIG. 6A. Itincludes a heartbeat-induced QRS complex that informally marks thebeginning of each cardiac cycle. FIG. 6B shows a PCG waveform, which ismeasured with the acoustic module and features the S1 and S2 heartsounds. FIG. 6C shows a PPG waveform, which is measured by the opticalsensor, and indicates volumetric changes in underlying capillariescaused by heartbeat-induced blood flow. The IPG waveform includes bothDC (Z₀) and AC (dZ(t)) components: Z₀ indicates the amount of fluid inthe chest by measuring underlying electrical impedance, and representsthe baseline of the IPG waveform; dZ(t), which is shown in FIG. 6D,tracks blood flow in the thoracic vasculature and represents thepulsatile components of the IPG waveform. The time-dependent derivativeof dZ(t)—dZ(t)/dt—includes a well-defined peak that indicates themaximum rate of blood flow in the thoracic vasculature, and is shown inFIG. 6E.

Each pulse in the ECG waveform (FIG. 6A) features a QRS complex thatdelineates a single heartbeat. Feature-detection algorithms operating infirmware on the neck-worn sensor calculate time intervals between theQRS complex and fiducial markers on each of the other waveforms. Forexample, the time separating a ‘foot’ of a pulse in the PPG waveform(FIG. 6C) and the QRS complex is referred to as PAT. PAT relates to BPand systemic vascular resistance. During a measurement, the neck-wornsensor calculates PAT and VTT which is a time difference betweenfiducial markers in waveforms other than ECG, e.g. the S1 or S2 pointsin a pulse in the PCG waveform (FIG. 6B) and the foot of the PPGwaveform (FIG. 6C). Or the peak of a pulse in the dZ(t)/dt waveform(FIG. 6E) and the foot of the PPG waveform (FIG. 6C). In general, anyset of time-dependent fiducials determined from waveforms other than ECGcan be used to determine VTT. Collectively, PAT, VTT, and othertime-dependent parameters extracted from pulses in the four physiologicwaveforms are referred to herein as ‘INT’ values. Additionally, firmwarein the neck-worn sensor calculates information about the amplitudes ofheartbeat-induced pulses in some of the waveforms; these are referred toherein as ‘AMP’ values. For example, the amplitude of the pulse in thederivative of the AC component of the IPG waveform ((dZ(t)/dt)max asshown in FIG. 6E) indicates the volumetric expansion and forward bloodflow of the thoracic arteries, and is related to SYS and thecontractility of the heart.

The general model for calculating SYS and DIA involves extracting acollection of INT and AMP values from the four physiologic waveformsmeasured by the neck-worn sensor. FIGS. 7A-F, for example, showdifferent INT and AMP values that may correlate to BP. INT valuesinclude the time separating R and S2 from a pulse in the PCG waveform(RS2, shown in FIG. 7A); the time separating R and the base of aderivative of a pulse from the AC component of the IPG waveform (RB,FIG. 7B); the time separating R and the foot of a pulse in the PPGwaveform (PAT, FIG. 7D); and the time separating R and the maximum of aderivative of a pulse from the AC component of the IPG waveform (RC,FIG. 7E). AMP values include the maximum value of a derivative of apulse from the AC component of the IPG waveform ((dZ(t)/dt)max, FIG.7C); and the maximum value of the DC component of the IPG waveform (Z₀,FIG. 7F). Any of these parameters may be used, in combination with acalibration defined below, to determine blood pressure.

The method for determining BP according to the invention involves firstcalibrating the BP measurement during a short initial period, and thenusing the resulting calibration for subsequent measurements. Thecalibration process typically lasts for about 5 days. It involvesmeasuring the patient multiple (e.g. 2-4) times with a cuff-based BPmonitor employing oscillometry, while simultaneously collecting the INTand AMP values like those shown in FIGS. 7A-F. Each cuff-basedmeasurement results in separate values of SYS, DIA, and MAP. Inembodiments, one of the cuff-based BP measurements may be coincidentwith a ‘challenge event’ that alters the patient's BP, e.g. squeezing ahandgrip, changing posture, or raising their legs. The challenge eventstypically impart variation in the calibration measurements; this canhelp improve the ability of the calibration to track BP swings.Typically, the neck-worn sensor and cuff-based BP monitor are inwireless communication with each other; this allows the calibrationprocess to be fully automated, e.g. information between the two systemscan be automatically shared without any user input. Processing the INTand AMP values, e.g. using the method shown in FIG. 9 and described inmore detail below, results in a ‘BP calibration’. This includes initialvalues of SYS and DIA, which are typically averaged from the multiplemeasurements made with the cuff-based BP monitor, along with apatient-specific model that is used in combination with selected INT andAMP values to cufflessly determine the patient's blood pressure. Thecalibration period (about 5 days), is consistent with a conventionalhospital stay; after this, the neck-worn sensor typically requires a newcalibration to ensure accurate BP measurements.

FIG. 9 is a flowchart that indicates how the BP calibration isdetermined, and how cuffless BP values are then calculated using the BPcalibration. The process starts by collecting calibration data (step150) that includes values of SYS and DIA. These data are collected alongwith INT and AMP values for each measurement. Typically, this process isrepeated four times, with one instance coinciding with a challengeevent, as described above. Using embedded firmware operating on theneck-worn sensor, the calibration data is then ‘fit’ with multiplelinear models (step 151) to determine which individual INT and AMPvalues best predict the patient's SYS and DIA values, as measured withthe cuff-based BP monitor. Here, the term ‘fit’ means using an iterativealgorithm, such as a Levenberg-Marquardt (LM) fitting algorithm, toprocess the INT/AMP values to estimate the calibration data. The LMalgorithm is also known as the damped least-squares (DLS) method, and isused to solve non-linear least squares problems. These minimizationproblems arise especially in least squares curve fitting. The INT andAMP values selected using the LM algorithm are those that yield theminimum error between the fits and calibration data (step 152); here,the error can be the ‘residual’ of the fit, or alternatively a root-meansquared error (RMSE) between the fit and the calculated data. Typically,two ideal INT/AMP values are selected with this process. Once selected,the two ideal INT/AMP values are then combined into a single,two-parameter linear model, which is then used to fit calibration dataonce again (step 153). The fitting coefficients that are determined fromthis fitting process, along with the average, initial values of SYS andDIA determined from the calibration data, represent the BP calibration(step 154). This process is done independently for SYS and DIA, meaningthat one set of INT/AMP values may be used for the BP calibration forSYS, and another set used for the BP calibration for DIA.

Once determined, the BP calibration is then used to calculate cufflessBP values going forward. Specifically, for a post-calibration cufflessmeasurement, the selected INT/AMP values (2 total) are measured from thetime-dependent ECG, IPG, PPG, and PCG waveforms. These values are thencombined in a linear model with the BP calibration (fitting coefficientsand average, initial values of SYS and DIA), which is then used tocalculate BP (step 155).

4. Clinical Results

The table 170 shown in FIG. 10 indicates the efficacy of this approachfor both SYS and DIA. Data in the table were collected using a clinicalstudy performed over a 3-day period with 21 subjects. In total, theclinical study was conducted over a 2-week period, starting in December2017 at a single study site in the greater San Diego area. Allmeasurements were made while the subjects rested in a supine position ina hospital bed. A BP calibration was determined on the first day of thestudy (Day 1) for each subject using the approach described above andshown in FIG. 9. Once the BP calibration was determined, the subject wasdismissed, and then returned 2 days later (Day 3) for a cuffless BPmeasurement. The BP calibration on Day 1 was used along with theselected INT/AMP values to determine cuffless BP values on Day 3, where10 measurements were made periodically over a period of about 2 hours,all while the subject was resting in a supine position. For mostsubjects, at least one of the 10 measurements featured a challengeevent, as described above, which typically elevated the subject's BP.And for each of the 10 measurements, cuffless BP values were compared toreference BP values measured with a ‘gold-standard technique’, which inthis case was a clinician measuring blood pressure using a techniquecalled auscultation, which is performed using a cuff-basedsphygmomanometer.

The table 170 includes the following columns:

Column 1—subject number

Column 2—maximum reference value of SYS (units mmHg)

Column 3—range in reference values of SYS (units mmHg)

Column 4—standard deviation calculated from the difference between thereference and cuffless values of SYS measured on Day 3 (10 measurementstotal, units mmHg)

Column 5—bias calculated from the difference between the reference andcuffless values of SYS measured on Day 3 (10 measurements total, unitsmmHg)

Column 6—selected INT/AMP values used in the cuffless measurement of SYS

Column 7—maximum reference value of DIA (units mmHg)

Column 8—range in reference values of DIA (units mmHg)

Column 9—standard deviation calculated from the difference between thereference and cuffless values of DIA measured on Day 3 (10 measurementstotal, units mmHg)

Column 10—bias calculated from the difference between the reference andcuffless values of DIA measured on Day 3 (10 measurements total, unitsmmHg)

Column 11—selected INT/AMP values used in the cuffless measurement ofDIA

As shown in the table 170, the average standard deviation and biascalculated from the difference between the reference and cuffless valuesof SYS measured on Day 3 were 7.0 and 0.6 mmHg, respectively. Thecorresponding values for DIA were 6.2 and −0.4 mmHg, respectively. Thesevalues are within those recommended by the U.S. FDA (standard deviationless than 8 mmHg, bias less than ±5 mmHg), and thus indicate that thecuffless BP measurement of the invention has suitable accuracy.

5. Alternative Embodiments

The neck-worn sensor described herein can have a form factor thatdiffers from that shown in FIG. 1. FIG. 11, for example, shows such analternate embodiment. Similar to the preferred embodiment describedabove, a patch sensor 210 in FIG. 11 features two primary components: acentral sensing/electronics module 230 worn near the center of thepatient's chest, and an optical sensor 236 worn near the patient's leftshoulder. Electrode leads 241, 242 measure bio-electrical signals forthe ECG and IPG waveforms and secure the central sensing/electronicsmodule 230 to the patient 12, similar to the manner as described above.A flexible, wire-containing cable 234 connects the centralsensing/electronics module 230 and the optical sensor 236. In this case,the central sensing/electronics module 230 features a substantiallyrectangular shape, as opposed to a substantially circular shape shown inFIG. 1. The optical sensor 236 includes two electrode leads 247, 248that connect to adhesive electrodes and help secure the patch sensor 210(and particularly the optical sensor 236) to the patient 12. The distalelectrode lead 248 connects to the optical sensor through anarticulating arm 245 that allows it to extend further out near thepatient's shoulder, thereby increasing its separation from the centralsensing/electronics module 230.

The central sensing/electronics module 230 features two halves 239A,239B, each housing sensing and electronic components that are separatedby a flexible rubber gasket 238. The central sensing/electronics module230 connects an acoustic module 232, which is positioned directly abovethe patient's heart. Flexible circuits (not shown in the figure)typically made of a Kapton® with embedded electrical traces) connectfiberglass circuit boards (also not shown in the figure) within the twohalves 239A, 239B of the central sensing/electronics module 230.

The electrode leads 241, 242, 247, 248 form two ‘pairs’ of leads,wherein one of the leads 241, 247 injects electrical current to measureIPG waveforms, and the other leads 242, 248 sense bio-electrical signalsthat are then processed by electronics in the centralsensing/electronics module 230 to determine the ECG and IPG waveforms.

The acoustic module 232 includes one or more solid-state acousticmicrophones (not shown in the figure, but similar to that shown inFIG. 1) that measure heart sounds from the patient 12. The opticalsensor 236 attaches to the central sensing/electronics module 30 throughthe flexible cable 234, and features an optical system (also not shownin the figure, but similar to that shown in FIG. 1) that includes anarray of photodetectors, arranged in a circular pattern, that surround aLED that emits radiation in the red and infrared spectral regions.During a measurement, sequentially emitted red and infrared radiationemitted from the LED irradiates and reflects off underlying tissue inthe patient's chest, and is detected by the array of photodetectors.

In other embodiments, an amplitude of either the first or second (orboth) heart sound is used to predict blood pressure. Blood pressuretypically increases in a linear manner with the amplitude of the heartsound. In embodiments, a universal calibration describing this linearrelationship may be used to convert the heart sound amplitude into avalue of blood pressure. Such a calibration, for example, may bedetermined from data collected in a clinical trial conducted with alarge number of subjects. Here, numerical coefficients describing therelationship between blood pressure and heart sound amplitude aredetermined by fitting data determined during the trial. Thesecoefficients and a linear algorithm are coded into the sensor for useduring an actual measurement. Alternatively, a patient-specificcalibration can be determined by measuring reference blood pressurevalues and corresponding heart sound amplitudes during a calibrationmeasurement, which proceeds an actual measurement. Data from thecalibration measurement can then be fit as described above to determinethe patient-specific calibration, which is then used going forward toconvert heart sounds into blood pressure values.

Both the first and second heart sounds are typically composed of acollection, or ‘packet’ of acoustic frequencies. Thus, when measured inthe time domain, the heart sounds typically feature a number of closelypacked oscillations within to the packet. This can make it complicatedto measure the amplitude of the heart sound, as no well-defined peak ispresent. To better characterize the amplitude, a signal-processingtechnique can be used to draw an envelope around the heart sound, andthen measure the amplitude of the envelope. One well-known technique fordoing this involves using a Shannon Energy Envelogram (E(t)), where eachdata point within E(t) is calculated as shown below:

$E_{average} = {{- \frac{1}{N}}{\sum\limits_{t = 1}^{N}\left\lbrack {{{PCG}^{2}(t)} \times {\log\left( {{PCG}^{2}(t)} \right)}} \right\rbrack}}$where N is the window size of E(t). In embodiments, other techniques fordetermining the envelope of the heart sound can also be used.

Once the envelope is calculated, its amplitude can be determined usingstandard techniques, such as taking a time-dependent derivative andevaluating a zero-point crossing. Typically, before using it tocalculate blood pressure, the amplitude is converted into a normalizedamplitude by dividing it by an initial amplitude value measured from anearlier heart sound (e.g., one measured during calibration). Anormalized amplitude means the relative changes in amplitude are used tocalculate blood pressure; this typically leads to a more accuratemeasurement.

In other embodiments, an external device may be used to determine howwell the acoustic sensor is coupled to the patient. Such an externaldevice, for example, may be a piezoelectric ‘buzzer’, or somethingsimilar, that generates an acoustic sound and is incorporated into theneck-worn sensor, proximal to the acoustic sensor. Before a measurement,the buzzer generates an acoustic sound at a known amplitude andfrequency. The acoustic sensor measures the sound, and then compares itsamplitude (or frequency) to other historical measurements to determinehow well the acoustic sensor is coupled to the patient. An amplitudethat is relatively low, for example, indicates that the sensor is poorlycoupled. This scenario may result in an alarm alerting the user that thesensor should be reapplied.

In still other alternative embodiments, the invention may use variationof algorithms for finding INT and AMP values, and then processing theseto determine BP and other physiological parameters. For example, toimprove the signal-to-noise ratio of pulses within the IPG, PCG, and PPGwaveforms, embedded firmware operating on the neck-worn sensor canoperate a signal-processing technique called ‘beatstacking’. Withbeatstacking, for example, an average pulse (e.g. Z(t)) is calculatedfrom multiple (e.g. seven) consecutive pulses from the IPG waveform,which are delineated by an analysis of the corresponding QRS complexesin the ECG waveform, and then averaged together. The derivative ofZ(t)—dZ(t)/dt—is then calculated over an 7-sample window. The maximumvalue of Z(t) is calculated, and used as a boundary point for thelocation of [dZ(t)/dt]_(max). This parameter is used as described above.In general, beatstacking can be used to determine the signal-to-noiseratio of any of the INT/AMP values described above.

In other embodiments, the BP calibration process indicated by the flowchart in FIG. 9 can be modified. For example, it may select more thantwo INT/AMP values to use for the multi-parameter linear fittingprocess. And the BP calibration data may be calculated with less than ormore than four cuff-based BP measurements. In still other embodiments, anon-linear model (e.g. one using a polynomial or exponential function)may be used to fit the calibration data.

In still other embodiments, a sensitive accelerometer can be used inplace of the acoustic sensor to measure small-scale, seismic motions ofthe chest driven by the patient's underlying beating heart. Suchwaveforms are referred to as seismocardiogram (SCG) and can be used inplace of (or in concert with) PCG waveforms.

These and other embodiments of the invention are deemed to be within thescope of the following claims.

What is claimed is:
 1. A sensor for measuring photoplethysmogram (PPG)and electrocardiogram (ECG) waveforms from a patient, the sensorcomprising: a primary housing, wherein during use the primary housing isconfigured to rest entirely on a middle of the patient's chest, theprimary housing comprising a first portion and a second portion, thefirst portion disposed above the second portion; a secondary housing,coupled to the primary housing via a flexible wire, the secondaryhousing including a heating element, a temperature sensor, and anoptical system, wherein the secondary housing is disposed adjacent to ashoulder, and wherein: the heating element is attached to a bottomsurface of the secondary housing so that it contacts and heats an areaadjacent to the shoulder; the temperature sensor is in direct contactwith the heating element; the optical system comprises a light sourceconfigured to generate optical radiation that irradiates the areaadjacent to the shoulder after it is heated by the heating element, anda photodetector configured to generate a PPG waveform by detectingradiation that reflects off the area; wherein the primary housingcomprises an ECG sensor comprising two electrode leads and an ECGcircuit, the ECG circuit configured to receive signals from theelectrode leads when the sensor is worn by the patient and, afterprocessing them, generate an ECG waveform; wherein the primary housingfurther comprises a processing system configured to analyze the ECGwaveform to identify a first fiducial marker comprised in the ECGwaveform, and based on the first fiducial marker, identify a secondfiducial marker comprised in the PPG waveform; and a closed-looptemperature controller comprised within the secondary housing and inelectrical contact with each of the heating element, the temperaturesensor, and the processing system, the closed-loop temperaturecontroller configured to: 1) receive a first signal from the temperaturesensor; 2) receive a second signal from the processing systemcorresponding to the second fiducial marker; 3) collectively process thefirst and second signals to generate a control parameter; and 4) controlan amount of heat generated by the heating element based on the controlparameter.
 2. The sensor of claim 1, wherein the software systemcomprised by the processing system is configured to determine a firstfiducial marker comprised by the ECG waveform that is one of a QRSamplitude, a Q-point, a R-point, an S-point, and a T-wave.
 3. The sensorof claim 1, wherein the software system comprised by the processingsystem is configured to determine a second fiducial marker that is oneof an amplitude of a portion of the PPG waveform, a foot of a portion ofthe PPG waveform, and a maximum amplitude of a mathematical derivativeof the PPG waveform.
 4. The sensor of claim 1, wherein a first electrodelead is connected to one side of the primary housing, and a secondelectrode lead is connected to an opposing side of the primary housing.5. The sensor of claim 4, further comprising a first cable and a secondcable, wherein the first cable connects a first electrode lead to theprimary housing, and the second cable connects a second electrode leadto the primary housing.
 6. The sensor of claim 1, further comprising asingle electrode patch comprising a first electrode region configured toattach to a first electrode lead, a second electrode region configuredto attach to a second electrode lead, and wherein, the secondary housinghas an opening configured to transmit optical radiation generated by theoptical system.
 7. The sensor of claim 1, wherein the closed-looptemperature controller comprises an adjustable voltage source, and isconfigured to control an amount of heat generated by the heating elementby adjusting the voltage source.
 8. The sensor of claim 7, wherein theclosed-loop temperature controller is configured to control the amountof heat generated by the heating element by adjusting an amplitude of avoltage generated by the voltage source.
 9. The sensor of claim 7,wherein the closed-loop temperature controller is configured to controlthe amount of heat generated by the heating element by adjusting afrequency of a voltage generated by the voltage source.
 10. The sensorof claim 7, wherein the closed-loop temperature controller is configuredto process the signal from the temperature sensor, and, in response,adjust a signal it applies to the resistive heater so that its resultingtemperature is between 40-45° C.
 11. The sensor of claim 1, wherein theheating element comprises a resistive heater.
 12. The sensor of claim11, wherein the resistive heater is a flexible film.
 13. The sensor ofclaim 12, wherein the resistive heater comprises a set of electricaltraces configured to increase in temperature when electrical currentpasses through them.
 14. The sensor of claim 12, wherein the flexiblefilm is a polymeric material.
 15. The sensor of claim 14, wherein thepolymeric material comprises Kapton®.
 16. The sensor of claim 1, whereinthe heating element is a metallic material.
 17. The sensor of claim 1,wherein the heating element is a source of electromagnetic radiation.18. A sensor for measuring photoplethysmogram (PPG) andelectrocardiogram (ECG) waveforms from a patient, the sensor comprising:a primary housing, wherein during use the primary housing is configuredto rest entirely on a middle of the patient's chest, the primary housingcomprising a first portion and a second portion, the first portiondisposed above the second portion; a secondary housing, coupled to theprimary housing via a flexible wire, the secondary housing including aheating element, a temperature sensor, and an optical system, whereinthe secondary housing is disposed adjacent to a shoulder, and wherein;the heating element is attached to a bottom surface of the secondaryhousing so that it contacts and heats an area adjacent to the shoulder;the temperature sensor is in direct contact with the heating element;the optical system comprises a light source configured to generateoptical radiation that irradiates the area adjacent to the shoulder, anda photodetector configured to generate a PPG waveform by detectingradiation that reflects off the area after it is heated by the heatingelement; wherein the primary housing comprises an ECG sensor comprisingtwo electrode leads and an ECG circuit, the ECG circuit configured toreceive signals from the electrode leads when the sensor is worn by thepatient and, after processing them, generate an ECG waveform; whereinthe primary housing further comprises a processing system configured tocollectively analyze the ECG and PPG waveforms and, in response,generate a control parameter; and a closed-loop temperature controllercomprised within the secondary housing and in electrical contact witheach of the heating element, the temperature sensor, and the processingsystem, the closed-loop temperature controller configured to receive thecontrol parameter and, in response, control an amount of heat generatedby the heating element.
 19. The sensor of claim 18, wherein the softwaresystem comprised by the processing system is configured to determine afirst fiducial marker comprised by the ECG waveform that is one of a QRSamplitude, a Q-point, a R-point, an S-point, and a T-wave.
 20. Thesensor of claim 18, wherein the software system comprised by theprocessing system is configured to determine a second fiducial markerthat is one of an amplitude of a portion of the PPG waveform, a foot ofa portion of the PPG waveform, and a maximum amplitude of a mathematicalderivative of the PPG waveform.
 21. The sensor of claim 18, wherein afirst electrode lead is connected to one side of the primary housing,and a second electrode lead is connected to an opposing side of theprimary housing.
 22. The sensor of claim 21, further comprising a firstcable and a second cable, wherein the first cable connects a firstelectrode lead to the primary housing, and the second cable connects asecond electrode lead to the primary housing.
 23. The sensor of claim18, further comprising a single electrode patch comprising a firstelectrode region configured to attach to a first electrode lead, asecond electrode region configured to attach to a second electrode lead,and wherein, the secondary housing has an opening configured to transmitoptical radiation generated by the optical system.
 24. The sensor ofclaim 18, wherein the closed-loop temperature controller comprises anadjustable voltage source, and is configured to control an amount ofheat generated by the heating element by adjusting the voltage source.25. The sensor of claim 24, wherein the closed-loop temperaturecontroller is configured to control the amount of heat generated by theheating element by adjusting an amplitude of a voltage generated by thevoltage source.
 26. The sensor of claim 24, wherein the closed-looptemperature controller is configured to control the amount of heatgenerated by the heating element by adjusting a frequency of a voltagegenerated by the voltage source.
 27. The sensor of claim 24, wherein theclosed-loop temperature controller is configured to process the signalfrom the temperature sensor, and, in response, adjust a signal itapplies to the resistive heater so that its resulting temperature isbetween 40-45° C.
 28. The sensor of claim 18, wherein the heatingelement comprises a resistive heater.
 29. The sensor of claim 28,wherein the resistive heater is a flexible film.
 30. The sensor of claim29, wherein the resistive heater comprises a set of electrical tracesconfigured to increase in temperature when current passes through them.31. The sensor of claim 29, wherein the flexible film is a polymericmaterial.
 32. The sensor of claim 31, wherein the polymeric materialcomprises Kapton®.
 33. The sensor of claim 18, wherein the heatingelement is a metallic material.
 34. The sensor of claim 18, wherein theheating element is a source of electromagnetic radiation.